n NR and SVR patients, with an AUC of 0.776 and sensitivity, specificity and positive predictive values of 57.8, 95.5 and 96.2%, respectively, with a cut-off value of 3.9. In conclusion, the present study demonstrated that circulating extracellular miR-21 and miR-122 levels in serum samples from HCV-4 patients can be used to differentiate between the responses of NR and SVR to PEG-IFN/RBV therapy. Moreover, miR-21 appears to have a higher predictive response power than miR-122. ~~ ~~ Non-alcoholic fatty liver disease is recognized as a hepatic phenotype of the metabolic syndrome. It encompasses a wide spectrum of liver impairment ranging from benign simple steatosis to non-alcoholic steatohepatitis, which can lead to cirrhosis and hepatocellular carcinoma. The “two-hit” hypothesis has been proposed as a potential mechanism underlying NASH, in which the first step involves the excessive accumulation of lipids in the liver, thereby sensitizing the liver to the second hits including oxidative stress, lipopolysaccharide, proinflammatory cytokines and adipocytokines. However, the precise mechanisms involved in the disease progression from simple steatosis to NASH and hepatocellular carcinoma are still unclear. Accordingly, specific and definitive therapeutic strategies against NASH have not been fully established. It is partly PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763871 because there are few animal models that reflect the pathophysiology of human NASH. Recently, we have reported that melanocortin 4 receptor-deficient mice fed high-fat diet develop a liver condition similar to human NASH, which is associated with obesity, insulin resistance and dyslipidemia. MC4R is a seven-transmembrane G protein-coupled receptor that is implicated in the regulation of food intake and body weight. Because MC4R expression is mainly expressed in the hypothalamus and other brain regions, it is likely that the hepatic phenotype in MC4R-KO mice results from loss of function of MC4R in the brain, rather than in the liver itself. Accordingly, MC4R-KO mice would provide a novel rodent model with which to investigate the progression from diet-induced hepatic steatosis to NASH. Using this model, we have reported PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19761601 a unique histological structure in the liver termed hepatic crown-like structures, in which HC-067047 web macrophages surround dead or dying hepatocytes with large lipid droplets. hCLS structurally resembles obesity-induced adipose tissue CLS, where sustained interaction between dead adipocytes and macrophages induces adipose tissue inflammation, thereby leading to systemic insulin resistance. Interestingly, the number of hCLS is positively correlated with the extent of liver fibrosis, and myofibroblasts and collagen deposition are observed nearby hCLS, suggesting the role of hCLS in the development of NASH. We also detected hCLS in the liver of NAFLD/NASH patients. On the basis of these observations, hCLS may be involved in disease progression from simple steatosis to NASH. Fish oil rich in n-3 polyunsaturated fatty acids such as eicosapentaenoic acid or n-3 PUFAs are clinically effective to treat hypertriglyceridemia. As a molecular mechanism, n-3 PUFAs improve hepatic lipid metabolism mainly by regulating transcription factors such as peroxisome proliferators-activated receptor and sterol regulatory element binding protein-1c. In addition, epidemiological and clinical trials have shown that n-3 PUFAs significantly reduce the incidence of coronary heart disease, probably through their pleiotropic effect including a